多聚二磷酸腺苷核糖合成酶抑制剂对血管紧张素Ⅱ诱导心脏成纤维细胞基质金属蛋白酶表达的影响  

Inhibition of poly(ADP-ribose) polymerase prevented angiotensin Ⅱ induced expression of matrix metalloprotease in cardiac fibroblast

作　　者：李小丽[1] 黄恺[1] 黄丹[1] 杨崇哲[1] 姚兰[1] 廖玉华[1] 

机构地区：[1]华中科技大学协和医院心内科华中科技大学同济医学院心血管病研究所,武汉430022

出　　处：《临床心血管病杂志》2008年第3期213-216,共4页Journal of Clinical Cardiology

基　　金：国家自然科学基金资助项目(No:30400175)

摘　　要：目的:观察多聚二磷酸腺苷核糖合成酶(PARP)抑制剂对血管紧张素Ⅱ(AngⅡ)刺激的乳鼠心脏成纤维细胞基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)和金属蛋白酶组织抑制剂-1(TIMP-1)基因转录的影响。方法:新生SD大鼠心脏成纤维细胞原代培养,传代。用PARP抑制剂——3-氨基苯甲酰胺(3-AB)预处理细胞,观察3-AB对AngⅡ诱导心脏成纤维细胞MMP-2、MMP-9及TIMP-1基因表达的影响。结果:AngⅡ刺激心脏成纤维细胞MMP-2、MMP-9及TIMP-1基因表达明显增加,成纤维细胞内PARP活性及PARP1的表达显著增强。使用3-AB抑制PARP1的活性及表达,可以明显降低AngⅡ诱导的心脏成纤维细胞MMP-2、MMP-9及TIMP-1基因表达的增加。结论:PARP在AngⅡ诱导的心脏重构过程中发挥了重要的调控作用。Objective：To study the effect of poly（ADP-ribose） polymerase（PARP） inhibitor on cardiac fibroblast treated by angiotensin Ⅱ （Ang Ⅱ ）. Method： Cultured 3rd passage cardiac fibroblasts were incubated with PARP inhibitor 3-aminobenzamide （3-AB） for 30 minutes first and then 0.1μmol/L Ang Ⅱ were added to the culture medium. The incubation time was 24 hours. We explored the reactive oxygen species（ROS）, the PARP activity and the expression of MMP-2, MMP-9 and TIMP-1 in cardiac fibroblast. Result： Ang Ⅱ induced ROS generation,induced PARP activation and PARP1 expression, 3-AB effectively prevented the expression of matrix MMP- 2, MMP-9 and TIMP-1 in cultured fibroblast treated with Ang Ⅱ. Conclusion：Inhibition of PARP activation prevented Ang Ⅱ induced transcriptional expression of MMP-2, MMP-9 and TIMP-1 in cultured fibroblast.

关 键 词：血管紧张素Ⅱ 多聚ADP核糖合成酶 心脏 成纤维细胞 基质金属蛋白酶 

分 类 号：R322.1[医药卫生—人体解剖和组织胚胎学]